The interferons have antimicrobial, antitumor, cell growth regulatory and immunomodulatory activities. They also affect differentiation. Their various activities are performed by proteins that are encoded by interferon-activatable genes. The murine gene 200 cluster consists of at least six interferon-activatable, structurally related genes. These arose in consequence of repeated duplications. They encode the six or more 200 family proteins. The best characterized of these are p202a and p204. Both proteins are also components of the machinery of muscle differentiation. Besides their inducibility by interferons the genes encoding p202a and p204 can also be transcribed by the muscle-specific MyoD protein (independently of interferons). The level of both proteins increases many fold during skeletal and heart muscle differentiation. p204 is required for the fusion of muscle myoblasts to myotubes. It triggers the fusion primarily by overcoming the inhibition of MyoD activity by the Id (inhibitor of differentiation) proteins. p202a and p204 also have antiproliferative activity, and p202a is strongly antiapoptotic. The subcellular locations of the proteins (nucleolar, nucleoplasmic and cytoplasmic) depend on the type and the state of differentiation of cells. Both proteins function primarily by binding and modulating the activities of numerous transcription factors and transcriptional inhibitors. The transcription factors affected by p202a include: AP2, E2F-1, E2F-4, MyoD, myogenin, NF-kB, c-Myc and p53. By binding UBF, p204 inhibits ribosomal RNA synthesis. In most, though not all cases, p202a and p204 inhibit the sequence-specific binding of the factors to DNA. In the case of c-Myc however, the binding of c-Myc by p202a inhibits c-Myc's interaction with max. We plan to continue our studies on the roles of the murine and human 200 family proteins in the control of cell proliferation and differentiation using genetic, biological and biochemical approaches.